The present invention relates to medical methods and devices. More particularly, the present invention relates to diagnostic devices that can be linked to remote data collection and evaluation centers.
Many clinical conditions require monitoring of the status of certain patent metabolic or biochemical parameters. Often, a single reading is insufficient for optimal medical care. Rather, a series of readings over time, combined with other elements of the patient""s activities and medical history, are preferable. Readings may be plotted versus time, and trends spotted. Aberrant readings may be understood as being a result of patient non-compliance with a set medical regimen, an unforeseen but understandable change in the patient""s metabolic status. Trends and aberrant readings may then be judged on the basis of medication and treatment algorithms appropriate to the patient""s condition, and treatment programs appropriately adjusted.
Although some medical conditions, such as elevated cholesterol levels, vary on a long enough time scale so that patients may be appropriately monitored and treated by infrequent visits to medical clinics, other medical conditions, such as diabetes, need for oral anticoagulants, blood pressure or heart conditions, etc. require such a high frequency of monitoring as to make clinic monitoring problematic. For medical conditions where high frequency monitoring is indicated, current trends in medical technology are to provide easy to use, portable, monitoring units (meters) for use in a patient""s home environment.
For the above reasons, it is highly useful if the meter has a capability to store data in an on-board meter database, and the ability to recall this stored data whenever the user so desires. Such on-board meter databases have become standard in the diagnostics industry.
Although for an increasing number of analytes, modem technology makes it feasible to perform accurate monitoring in a non-clinical (home) environment, the problem of interpreting the results persists. The algorithms used to adjust patient treatment are often complex, and may require experienced medical judgment. This will obviously not be constantly available in a home environment. Thus methods of conveying data obtained in a non-clinical setting, to a central location where clinical judgment is available, either in the form of preset algorithms, or by on-site clinicians, are of considerable practical interest. Such methods are commonly referred to as telemetry or telemedicine.
A variety of telemedicine methods have been described and practiced. The most common methodologies proposed are schemes for first collecting and storing data using an instrument on-site with the patient. On an occasional basis, telecommunications links are established with clinicians or automated instrumentation at a central, decision making, location, and the stored data is then transferred. At the central location, this data is then processed. Medical opinions may then be relayed to where they are most useful.
Diabetics are one class of patients in need of such capability. For example, as taught by U.S. Pat. No. 4,731,726; diabetic patients may monitor their blood glucose levels with a blood glucose meter that contains an internal database of past readings, and in conjunction with remote communications linkages, work with clinicians to optimally manage their disease. Similarly, U.S. Pat. No. 4,712,562 discloses methods for the remote monitoring of blood pressure.
U.S. Pat. No. 5,704,366 teaches methods for interfacing a patient side system with a remote central database system, using device specific ID codes (essentially a meter serial number) that uniquely identifies a particular remote interface device.
U.S. Pat. No. 5,704,366 teaches methods for rearranging a database of readings, reserved for the meter""s internal data storage and recall purposes, in order to facilitate their transmission over a communications link.
U.S. Pat. No. 5,704,366 teaches methods in which the micro-controller on the patient-side meter is coupled to a patient-side telecommunication interface that can transmit analog signals to a remote computer.
U.S. Pat. No. 5,724,580 teaches methods of automatically generating management and prognosis reports and recommending therapy for a patient based on analysis of the downloaded data.
U.S. Pat. No. 3,820,028 teaches digital methods of DTMF decoding.
U.S. Pat. No. 4,484,035 teaches digital methods of DTMF decoding.
U.S. Pat. No. 4,087,638 teaches a DTMF Communication system.
U.S. Pat. No. 5,408,529 teaches a DTMF detector operable in the presence of speech or background noise.
U.S. Pat. No. 5,408,520 teaches conditional methods of switching between a land line telecommunications link, and a cellular communications link, involving the standard AT modem command set, depending upon battery status.
Of the various classes of patients, patients on oral anticoagulants, such as warfarin, have a particular need for a simple, easy to use system that combines accurate diagnostics and telemedicine capability. Such patients may include individuals with deep vein thrombosis, atrial fibrillation, artificial heart valves, myocardial infarction, hematologic disorders such as protein xe2x80x9cSxe2x80x9d or xe2x80x9cCxe2x80x9d deficiency, or activated protein C resistance, and many other medical indications. Such patients must maintain their blood coagulation status, monitored by prothrombin time testing, within a narrow therapeutic window. Too little anticoaguation can result in stroke or pulmonary embolism, while too much anticoaguation can result in bleeding or hemorrhage.
Warfarin is a vitamin K antagonist, and is absorbed by the gastrointestinal system to a variable amount depending upon the patient""s diet or gastrointestinal status. Patient response to any given dose of warfarin is highly variable between patients. Warfarin""s pharmokinetics are such that the effective half-life of the drug is several days. Thus prothrombin-time trend analysis, in conjunction with clinical inquiry as to changes in a patient""s diet or general condition, play an important role in managing this drug.
A number of different simple instruments to enable easy assessment of prothrombin time levels in a non-clinical setting have been proposed. For example, U.S. Pat. No. 4,849,340 teaches small disposable cartridge chambers containing dry thromboplastin and magnetic microparticles. The oscillation of the magnetic particles induced by a magnetic field is observed by optical means. Blood is introduced to the chamber, and the length of time required for the thromboplastin mediated blood coagulation to change the optical oscillation signature is proportional to the prothrombin time of the blood sample.
U.S. Pat. No. 5,300,779 teaches a small disposable cartridge chamber containing dry thromboplastin. Blood is introduced to the chamber, and is induced to migrate by capillary action. The movement of blood is observed by laser light scattering techniques. The time elapsed between the time that blood is introduced to the chamber, and the time required for thromboplastin mediated blood coagulation to change the laser light scattering signature, is proportional to the prothrombin time of the blood sample.
U.S. Pat. No. 5,302,348 teaches an alternate type of small disposable cartridge containing capillary tubes and dry thromboplastin. Blood is introduced to the capillary tubes, and the blood induced to move by variations in air pressure. This movement is also observed by optical means. The time elapsed between the application of blood, and the onset of resistance to movement, is proportional to the prothrombin time of the sample.
U.S. Pat. Nos. 5,344,754; 5,418,131; 5,418,143; 5,580,744; incorporated herein by reference, teach a dry reagent xe2x80x9ctest stripxe2x80x9d containing thromboplastin and a fluorescent thrombin substrate reporter molecule. Blood is applied to the test strip. The thromboplastin interacts with the blood sample, producing thrombin, which activates the fluorescent reporter molecule. The time elapsed between the application of blood, and the onset of fluorescence, is proportional to the prothrombin time of the sample.
For these reasons, it is medically useful for patients on oral anticoagulants to have access to simple, easy to use, prothrombin time meters with both on-board databases, and robust, simple, telemedicine capability.
Although telemedicine capability is obviously highly desirable, many patients in need of such services are frequently elderly and have diminished capability to use sophisticated telecommunications equipment. Telecommunications linkages to such patient""s homes may be low-grade telephone lines, often prone to noise and static. It is also difficult for unskilled patients to hook up meters to directly to telecommunications equipment. Frequently, telephone networks employ proprietary digital encoding schemes, that make it difficult to interface by direct electrical means. For such reasons, simplified and robust schemes to enable easy implementation of telemedicine capability under adverse conditions are of high utility.
One method that avoids electrical compatibility issues is direct acoustic linkage, in which a meter is brought in close proximity to a telephone handset. This eliminates the need for any direct electrical linkage between the meter and a telecommunications unit, and additionally gets around problems caused by incompatible equipment. Acoustic coupling has its own set of problems, however, particularly with high-speed modem transmissions. Background noise can distort complex modem acoustic signals. Thus with typical modem technology, mechanical coupler devices to muffle ambient noise, such as the devices taught in U.S. Pat. Nos. 3,619,507 and 4,252,996 are often required in order to get reliable data transmission. Such devices impose a burden on unskilled users, however.
One of the most robust acoustic methods used to communicate small amounts of data is the standard xe2x80x9ctouch tonexe2x80x9d xe2x80x9cDual Tone Multi Frequencyxe2x80x9d or DTMF methodology. This methodology is able to communicate hexadecimal digits (the numbers 0-9 and letters A-F) by a combination of two audio frequencies. DTMF technology is widely used in the communications industry because its low speed and simple tonal signals allow DTMF signals to be discerned in the highest noise practicable environments.
The standard DTMF frequency matrix is shown in table 1 below:
Because of its extreme robustness and resistance to outside noise, DTMF devices may operate reliably with close, but not perfect acoustic linkage. This is a significant advantage for unskilled users who wish to use a simple meter in conjunction with standard telephone lines, with a minimum of extra equipment or effort. A user may simply bring a meter reasonably close to a broad variety of telephone handsets, and obtain good results with out extra equipment.
Although the methods here can work with the standard DTMF frequencies, it is obvious that alternate frequencies can work as well. In some situations, this may be desirable; to avoid interference with standard DTMF signals. Here DTMF is used in the broadest sense to describe any dual tone multifrequency signaling method, and is not meant to be construed to follow only the specific frequencies as outlined in table 1.
Although DTMF methods are robust, they are extremely slow. A typical DTMF session can transmit about 10 hexadecimal digits a second. Thus, whenever possible, it is preferable to communicate by higher speed linkages, and reserve DTMF as a low speed fallback method.
Thus it is desirable if, before initiating a DTMF session, a meter first automatically checks if a higher speed telecommunications link exists, and if so automatically uses it. One common form of higher speed telecommunications link, suitable for home use, is standard modem technology.
Standard modem technology is well suited for these purposes. In addition to data transmission, it is useful in some situations if a telecommunications link can also provide a voice channel so that numeric readings can be annotated with patient comments. Voice linkage also allows advice from a central location can be relayed to a patient in a timely manner. Fortunately, standard modems have this dual voice/data capability. Typically, commercial modems have a connection to an outside telephone line, a local telephone handset, and a RS232 data line. When the modem is inactive, the local telephone handset is connected to the outside telephone line. When the modem is active, the local handset is disconnected, and the modem takes control of the telephone line.
Typically, modems are controlled by use of a standard xe2x80x9cATxe2x80x9d command set. A modem, located either internal or external to the meter, may be queried as to if it is hooked up to a telecommunications link by a set of xe2x80x9cATxe2x80x9d commands.
Thus before initiating a fallback DTMF session, it is useful if a meter first checks for the existence of a higher speed modem link using standard modem xe2x80x9cATxe2x80x9d commands. If no such higher speed link is found, the meter could then fall back to DTMF use.
Patients also have a need to review and post readings from a meter""s database. Typically, meters have user input means, such as a button, which can be activated to allow local viewing of a meter""s database. To keep a meter""s user interface as simple as possible, in some instances it may be desirable to allow the same user input means used to view a database locally to also engage a meter""s automatic search for a high speed telecommunications link. Assuming such search is quick, then the user is not inconvenienced, and the meter interface is kept simple.
Since DTMF fallback is slow and noisy, however, it is usually preferable to have some means of distinguishing a user""s desire for local memory playback from the user""s desire to establish a telecommunications link. This can be done either by a different user input means, such as a separate button. Alternatively, a single user input means can be used in a distinct mode. For example, a user can hold a button down for a short period of time when local playback is desired, and a longer period of time when a telecommunications link is desired.
In one embodiment of this invention, a meter consists of a local database, and a port for an external modem, so that upon activation of a user recall button, the meter begins a search for an external modem via a set of xe2x80x9cATxe2x80x9d commands.
In a second embodiment of this invention, a meter consists of a local database, an internal modem, and a port for an external telephone line. Upon activation of a user recall button, the meter queries the status of the internal modem hook-up to the external telephone line via a set of xe2x80x9cATxe2x80x9d commands.
Other embodiments are possible. For example, the meter may incorporate a speaker, or both a speaker and a microphone, and means to either send, or send and receive, acoustic signals such as modem or DTMF signals. Thus a DTMF session could be uni-directional, from meter to remote location only, bi-directional between both the meter and the remote location.
Using modem technology, low cost meter systems may be built around commercially available microcontrollers, such as the Texas Instruments MSP430, that combine on one chip, many discrete functions as Analog/Digital conversion, Liquid Crystal Display drivers, and sufficient processing power to drive digital DTMF encoders and decoders. Such techniques are described in xe2x80x9cGeneration and Recognition of DTMF signals with the Microcontroller MSP430, Robert Siwy, Texas Instruments Deutschland GmbH report SLAAE16, October 1997,xe2x80x9d incorporated herein by reference.
In a typical communications session, the user takes the telephone off-hook, and manually or automatically dials into a central database location. The operator at the central location (either human or machine) picks up the line. The meter user then commences a dialog with the central location, in which the meter user receives instructions from the central location, and in turn verbally tells the central location details of the patients medical status, meter status, etc. The central location then prompts the user to press his/her user-input means, such as a memory recall button, upon hearing a carrier tone from the central location. The central location then switches to a modem carrier tone, or a DTMF carrier tone.
Upon hearing the tone, the meter user pushes the memory recall button on the meter. The meter first sends out a series of commands to initialize the meter""s modem or DTMF unit. The meter then listens for a proper set of return characters from the central location. If the proper set of return characters is not received within a pre-defined time-out period, the meter instructs the modem/DTMF to turn off (return to on-hook status). The user retains or regains the voice linkage with the central location, and the meter then proceeds to recall previous data on the meter""s own internal display. The central location can either elect to discuss the displayed data verbally with the meter user, or alternatively prompt the user to attempt a telemedicine session by resetting the meter, and once again pressing the memory recall button. In either event, a voice linkage with the central location persists until the user chooses to hang up the telephone.
Here the term xe2x80x9cbuttonxe2x80x9d is used to describe the means used to communicate to the meter that data recall is desired. This may include push buttons, membrane keypads, touch-screen, light pen, and other touch activated sensors.
If a positive data linkage is established with the remote location, the central location then proceeds to download the user identification data from the user data memory, and to determine how many tests have been performed since the last telemedicine session. This can be done by both downloading and examining the status of the user identification and test counter, and comparing this test counter to the number previously stored in a database at the central location. In either event, the central location then calculates how many tests it needs to download, and sends the commands to the meter to retrieve and transmit the appropriate test records. The remote telemedicine session may then optionally choose to update the meter""s handshake memory record of the last test number successfully transmitted.
Upon receiving the data, the central location then performs checksum tests to be sure that the data was accurately transmitted, and automatically requests resends of corrupted data as appropriate. The central location can then analyze the data, either automatically, manually, or a combination of the two, for one or more key user performance parameters. These parameters may include:
Proper use of electronic controls or liquid controls
Electronic controls and liquid controls within proper range
Test results within pre-specified clinical limits
Trend analysis on the test results
Test results performed at the desired times and frequencies
Meter clock properly set
Meter modes and calibration properly set
Upon analysis, the central location may then manually, or automatically, advise the user to maintain or change certain practices. For example, advise for more frequent use of controls, more frequent testing, or advise that test results are either outside, or trending to outside, pre-specified clinical limits. The central location may then pass patient results on to a clinician, or alternatively, an on-site clinician may advise as to the next course of action.
For oral anticoagulant treatment, it is particularly advantageous to link voice data with numeric downloaded data as part of the patient record. As an example, oral anticoagulant monitoring is complex and highly individualized. Subtle changes in a patients diet, health status, or activities may perturb results.
Such linkage may be done immediately, as a patient interacts with a live operator at the central location. Alternatively, the patient voice data may be automatically stored by the central location, and reviewed by a human or automated operator at a later time.
Certain modifications to this basic telemedicine process may also be practiced. For example, the meter may contain one or more telephone numbers or access codes within its internal xe2x80x9chandshakexe2x80x9d memory, and be pre-set to dial into a central location without direct user intervention. The modem or other telemedicine electronics may be built in to the test meter body, or alternatively be external to the meter body, and connected by either a data cable or wireless connection, such as an infra red or radio link.
Example telemedicine session:
Weekly session from a patient assigned to use a prothrombin time meter twice weekly. During this week, the patient ran controls to test meter performance. The patient deviated from his diet, and ate a large salad on Wednesday. The patient has otherwise been compliant with his medication.
Patient hooks meter up to modem unit, and dials a touch-tone telephone to the central location. The central location has caller ID.
Central location: Establishes voice link and confirms patient identity.
Patient: Confirms identity, and explains reason for call.
Central location: Prompts patient to ready meter for data transmission.
Patient: Waits to hear tone, and then presses his meter""s xe2x80x9cMxe2x80x9d button. The meter displays xe2x80x9cTEL-on,xe2x80x9d and establishes a two-way data session with the central location. When this is established, the meter then displays xe2x80x9cCOM-on.xe2x80x9d
Central location computer: Sends command to download data from the meter""s user data area, containing the patient""s ID code. The central computer then reads a number of data records from the meter""s data storage memory. Finally, the central computer checks the time and date of the user""s meter, and confirms that it is accurate. If it is not, the central computer updates the meter""s clock to the correct time and date. The data is then displayed on a computer screen so that a human operator at the central location can then view the recent data. The central location computer then sends a command back to the meter ending the data session, and reestablishing two-way voice communication.
Central location operator: Talks to patient, and reinforces proper use of control testing to ensure good system performance. Questions patient about an aberrant reading.
Patient: Initially unsure why a downloaded reading is aberrant.
Central location operator: Questions patient about possible changes in diet or daily routine.
Patient: After some thought, recalls recent change in diet.
Central location operator: Reviews standing orders from patient""s physician. Quotes from the standing order that for this situation, no change in dosage is recommended. Discontinue the changed diet, and repeat testing for three days. If the INR readings are still aberrant, to telephone back with the results within three days. The central location then makes a note of the call and advice in a centralized database, and sets a reminder call for three days in the future.